title: Alemtuzumab for the prevention and treatment of graft-versus-host disease.
abstract: Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen, which is expressed on the surface of various hematopoietic cells such as B and T lymphocytes, and has been widely used for preventing acute graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (SCT). Administration of 100 mg alemtuzumab before transplantation has resulted in a low incidence of acute GVHD in HLA-matched and mismatched transplantation from either related or unrelated donors. However, because alemtuzumab could remain in the blood at the lympholytic level 1-2 months after transplantation, immune reconstitution was substantially delayed, leading to a high incidence of viral infection and relapse. A dose reduction of alemtuzumab was attempted in a reduced-intensity conditioning setting to facilitate immune reconstitution, and this resulted in earlier immune reconstitution, but the clinical benefits were unclear. The dose of alemtuzumab and the timing of its administration should be optimized to maximize the benefit of acute GVHD suppression and minimize the risk of infection and relapse. Another strategy to facilitate immune reconstitution and augment anti-tumor effects is donor cell infusion of T and NK cells. Although there is accumulating evidence regarding the use of alemtuzumab for acute GVHD prevention, information on the salvage treatment for steroid-refractory acute and chronic GVHD is still limited.
authors.affiliation: Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 1100, Durham, NC, 27705, USA.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Bone Marrow Transplantation Program, Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lopez
authors.affiliation: Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, 2400 Pratt Street, Suite 1100, Durham, NC, 27705, USA. rizzi003@mc.duke.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D000074301:CD52 Antigen; D002986:Clinical Trials as Topic; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D017710:Lymphocyte Transfusion; D009894:Opportunistic Infections / Q000517:prevention & control; D012008:Recurrence; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab